Abstract

LHF-535 is a small molecule antiviral currently in development for the treatment of Lassa fever, a zoonotic disease endemic in West Africa that generates significant morbidity and mortality. Current treatment options are inadequate, and there are no approved therapeutics or vaccines for Lassa fever. LHF-535 was evaluated in a lethal guinea pig model of Lassa pathogenesis, using once-daily administration of a fixed dose (50 mg/kg/day) initiating either 1 or 3 days after inoculation with a lethal dose of Lassa virus. LHF-535 reduced viremia and clinical signs and protected all animals from lethality. A subset of surviving animals was rechallenged four months later with a second lethal challenge of Lassa virus and were found to be protected from disease. LHF-535 pharmacokinetics at the protective dose in guinea pigs showed plasma concentrations well within the range observed in clinical trials in healthy volunteers, supporting the continued development of LHF-535 as a Lassa therapeutic.

Details

Title
Lassa antiviral LHF-535 protects guinea pigs from lethal challenge
Author
Cashman, Kathleen A. 1 ; Wilkinson, Eric R. 1 ; Posakony, Jeffrey 2 ; Madu, Ikenna G. 3 ; Tarcha, Eric J. 4 ; Lustig, Kurt H. 4 ; Korth, Marcus J. 4 ; Bedard, Kristin M. 5 ; Amberg, Sean M. 4 

 U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Virology Division, Frederick, USA (GRID:grid.416900.a) (ISNI:0000 0001 0666 4455) 
 Kineta, Inc., Seattle, USA (GRID:grid.429501.b); AltPep, Seattle, USA (GRID:grid.429501.b) 
 Kineta, Inc., Seattle, USA (GRID:grid.429501.b); Lyell Immunopharma, Seattle, USA (GRID:grid.510010.5) 
 Kineta, Inc., Seattle, USA (GRID:grid.429501.b) 
 Kineta, Inc., Seattle, USA (GRID:grid.429501.b); Sutro Biopharma, South San Francisco, USA (GRID:grid.510077.4) (ISNI:0000 0004 1799 1576) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2737811747
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.